CpG的结构基础和通过Toll-like受体9进行抑制性DNA识别
Umeharu Ohto1, Takuma Shibata2, Hiromi Tanji1
1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nature
|February 18, 2015
概括
收费类受体9 (TLR9) 的结构洞察力揭示了它如何与细菌DNA结合以触发天生的免疫力. 了解这些相互作用是开发新免疫疗法的关键.
科学领域:
- 免疫学 免疫学 免疫学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 天生的免疫是人体对病原体的初始防御.
- 收费类受体 (TLRs) 检测病原体模式以激活免疫反应.
- TLR9特别识别细菌和病毒DNA动机 (CpG-DNA).
研究的目的:
- 阐明通过CpG-DNA激活TLR9的分子机制.
- 确定TLR9识别agonistic和抑制DNA的结构基础.
主要方法:
- 使用X射线结晶学来确定TLR9在不同状态中的结构.
- 这项研究分析了TLR9的结构:未结合,结合对抗性CpG-DNA和结合抑制性DNA (iDNA).
主要成果:
- 对抗性CpG-DNA结合诱导了一个对称的2:2 TLR9-CpG-DNA复合体.
- 抑制性DNA (iDNA) 结合导致单体TLR9结构.
- 通过来自两个不同的TLR9原体的特定域识别了cpG-DNA.
- 结合TLR9上的形表面的iDNA,由其茎环结构促进.
结论:
- 确定的结构为TLR9功能提供了分子基础.
- 这些发现增强了对TLR9如何感知外来DNA的理解.
- 这些结构性见解可以指导新型免疫调节剂的开发.
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